TY - JOUR
T1 - Lenvatinib with or Without Everolimus in Patients with Metastatic Renal Cell Carcinoma After Immune Checkpoint Inhibitors and Vascular Endothelial Growth Factor Receptor-Tyrosine Kinase Inhibitor Therapies
AU - Wiele, Andrew J.
AU - Bathala, Tharakeswara K.
AU - Hahn, Andrew W.
AU - Xiao, Lianchun
AU - Duran, Munevver
AU - Ross, Jeremy A.
AU - Jonasch, Eric
AU - Shah, Amishi Y.
AU - Campbell, Matthew T.
AU - Msaouel, Pavlos
AU - Tannir, Nizar M.
N1 - Funding Information:
The authors acknowledge the patients and caregivers who participated and contributed to this study. This study was approved by the Internal Review Board/Ethics Committee of The University of Texas, MD Anderson Cancer Center. There was no writing assistance provided in the preparation of this manuscript. This work was supported in part by Cancer Center Support (Core) grant P30 CA016672 from the National Cancer Institute, National Institutes of Health, to The University of Texas MD Anderson Cancer Center. Pavlos Msaouel is supported by a Young Investigator Award from the Kidney Cancer Association, a Career Development Award from the American Society of Clinical Oncology, by a Concept Award from the U.S. Department of Defense, by a KCCure Research Award, and by the MD Anderson Khalifa Scholar award.
Funding Information:
The authors acknowledge the patients and caregivers who participated and contributed to this study. This study was approved by the Internal Review Board/Ethics Committee of The University of Texas, MD Anderson Cancer Center. There was no writing assistance provided in the preparation of this manuscript. This work was supported in part by Cancer Center Support (Core) grant P30 CA016672 from the National Cancer Institute, National Institutes of Health, to The University of Texas MD Anderson Cancer Center. Pavlos Msaouel is supported by a Young Investigator Award from the Kidney Cancer Association, a Career Development Award from the American Society of Clinical Oncology, by a Concept Award from the U.S. Department of Defense, by a KCCure Research Award, and by the MD Anderson Khalifa Scholar award.
Publisher Copyright:
© 2021 AlphaMed Press
PY - 2021/6
Y1 - 2021/6
N2 - Introduction: Lenvatinib (Len) plus everolimus (Eve) is an approved therapy for metastatic renal cell carcinoma (mRCC) after first-line vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs), but limited data exist on the efficacy of Len ± Eve after progression on immune checkpoint inhibitors (ICIs) and VEGFR-TKIs. Methods: We retrospectively reviewed the records of patients with mRCC at our institution who were treated with Len ± Eve after ICI and VEGFR-TKI. A blinded radiologist assessed objective response as defined by RECIST version 1.1. Descriptive statistics and the Kaplan-Meier method were used. Results: Fifty-five patients were included in the analysis. Of these patients, 81.8% had clear-cell histology (ccRCC), and 76.4% had International Metastatic RCC Database Consortium intermediate-risk disease. Median number of prior therapies was four (range, 2–10); all patients had prior ICIs and VEGFR-TKIs, and 80% were previously treated with ICI and at least two VEGFR-TKIs, including cabozantinib. One patient (1.8%) achieved a complete response, and 11 patients (20.0%) achieved a partial response, for an overall response rate (ORR) of 21.8%; 35 patients (63.6%) achieved stable disease. In all patients, median progression-free survival (PFS) was 6.2 months (95% confidence interval [CI], 4.8–9.4) and median overall survival (OS) was 12.1 months (95% CI, 8.8–16.0). In patients with ccRCC, ORR was 24.4%, PFS was 7.1 months (95% CI, 5.0–10.5), and OS was 11.7 months (95% CI, 7.9–16.1). 50.9% of patients required dose reductions and 7.3% discontinued treatment because of toxicity. Conclusion: Len ± Eve demonstrated meaningful clinical activity and tolerability in heavily pretreated patients with mRCC after disease progression with prior ICIs and VEGFR-TKIs. Implications for Practice: As the therapeutic landscape for patients with metastatic renal cell carcinoma continues to evolve, this single-center, retrospective review highlights the real-world efficacy of lenvatinib with or without everolimus in heavily pretreated patients. This article supports the use of lenvatinib with or without everolimus as a viable salvage strategy for patients whose disease progresses after treatment with immune checkpoint inhibitors and vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapies, including cabozantinib.
AB - Introduction: Lenvatinib (Len) plus everolimus (Eve) is an approved therapy for metastatic renal cell carcinoma (mRCC) after first-line vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs), but limited data exist on the efficacy of Len ± Eve after progression on immune checkpoint inhibitors (ICIs) and VEGFR-TKIs. Methods: We retrospectively reviewed the records of patients with mRCC at our institution who were treated with Len ± Eve after ICI and VEGFR-TKI. A blinded radiologist assessed objective response as defined by RECIST version 1.1. Descriptive statistics and the Kaplan-Meier method were used. Results: Fifty-five patients were included in the analysis. Of these patients, 81.8% had clear-cell histology (ccRCC), and 76.4% had International Metastatic RCC Database Consortium intermediate-risk disease. Median number of prior therapies was four (range, 2–10); all patients had prior ICIs and VEGFR-TKIs, and 80% were previously treated with ICI and at least two VEGFR-TKIs, including cabozantinib. One patient (1.8%) achieved a complete response, and 11 patients (20.0%) achieved a partial response, for an overall response rate (ORR) of 21.8%; 35 patients (63.6%) achieved stable disease. In all patients, median progression-free survival (PFS) was 6.2 months (95% confidence interval [CI], 4.8–9.4) and median overall survival (OS) was 12.1 months (95% CI, 8.8–16.0). In patients with ccRCC, ORR was 24.4%, PFS was 7.1 months (95% CI, 5.0–10.5), and OS was 11.7 months (95% CI, 7.9–16.1). 50.9% of patients required dose reductions and 7.3% discontinued treatment because of toxicity. Conclusion: Len ± Eve demonstrated meaningful clinical activity and tolerability in heavily pretreated patients with mRCC after disease progression with prior ICIs and VEGFR-TKIs. Implications for Practice: As the therapeutic landscape for patients with metastatic renal cell carcinoma continues to evolve, this single-center, retrospective review highlights the real-world efficacy of lenvatinib with or without everolimus in heavily pretreated patients. This article supports the use of lenvatinib with or without everolimus as a viable salvage strategy for patients whose disease progresses after treatment with immune checkpoint inhibitors and vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapies, including cabozantinib.
KW - Cabozantinib
KW - Immune checkpoint inhibitors
KW - Lenvatinib
KW - Lenvatinib plus everolimus
KW - Renal cell carcinoma
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U2 - 10.1002/onco.13770
DO - 10.1002/onco.13770
M3 - Article
C2 - 33792094
AN - SCOPUS:85104762649
SN - 1083-7159
VL - 26
SP - 476
EP - 482
JO - Oncologist
JF - Oncologist
IS - 6
ER -